Oncolytics Biotech Inc. (ONCY)

[onco_investor]

New Clinical Trial Announced Multiple Myeloma

http://clinicaltrials.gov/ct2/show/NCT02101944?term=reolysin&rank=16

New trial Sponsored by the US NCI - posted March 28, 2014
Principal Investigator: Craig Hofmeister Ohio State University

Purpose
This pilot clinical trial studies viral protein production after dexamethasone, wild-type reovirus, and carfilzomib in treating patients with multiple myeloma. Drugs used in chemotherapy, such as dexamethasone and carfilzomib, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. A virus called wild-type reovirus may be able to kill cancer cells without damaging normal cells and seems to work best when given with chemotherapy. Giving wild-type reovirus with chemotherapy may kill more cancer cells and be an effective treatment for multiple myeloma.

Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
Reovirus replication as measured by reovirus capsid protein production [ Time Frame: Days 1 and 9 of first course ] [ Designated as safety issue: No ]
Adverse events based on Common Terminology Criteria for Adverse Events (CTCAE) criteria [ Time Frame: Up to 4 weeks post treatment ] [ Designated as safety issue: Yes ]
Tolerability (number and severity of toxicity incidents) of combination carfilzomib and wild-type reovirus assessed by CTCAE version 4 [ Time Frame: Up to 4 weeks post treatment ] [ Designated as safety issue: Yes ]
Frequency distributions and other descriptive measures will form the basis of the analysis of these variables.

Number of patients who required dose modifications and/or dose delays in subsequent cycles [ Time Frame: Up to 4 weeks post treatment ] [ Designated as safety issue: Yes ]
Proportion of patients who go off treatment due to adverse reactions or refuse further treatment for lesser toxicities that inhibit their willingness to continue participation on the trial [ Time Frame: Up to 4 weeks post treatment ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
Number and percentage of subjects experiencing objective response [ Time Frame: Up to 4 weeks post treatment ] [ Designated as safety issue: No ]
Summary statistics will be computed for baseline biomarkers. The absolute and percent change from baseline will be calculated for each subsequent measurement. Summary statistics will be computed for each collection time point. The objective response rate will be analyzed by using a 95% confidence interval for the proportion responding at trial closure in the treated population.

Clinical benefit endpoint described as that portion of patients experiencing complete response (CR), very good partial response (VGPR), or partial response (PR) [ Time Frame: Up to 4 weeks post treatment ] [ Designated as safety issue: No ]
The objective response rate will be analyzed by using a 95% confidence interval for the proportion responding at trial closure in the treated population.

Duration of response [ Time Frame: Duration from first observation of partial response to the time of disease progression, up to 4 weeks post treatment ] [ Designated as safety issue: No ]
This time-to-event distribution will be evaluated using the methods of Kaplan and Meier, with a focus on graphical evaluation as well as early timepoint and median estimates of survival distributions.

Progression free survival [ Time Frame: Duration from start of treatment to disease progression or death, regardless of cause of death, whichever comes first, up to 6 months ] [ Designated as safety issue: No ]
This time-to-event distribution will be evaluated using the methods of Kaplan and Meier, with a focus on graphical evaluation as well as early timepoint and median estimates of survival distributions.

Time to progression [ Time Frame: Time from the start of the treatment until the criteria for disease progression are met, up to 4 weeks post treatment ] [ Designated as safety issue: No ]
This time-to-event distribution will be evaluated using the methods of Kaplan and Meier, with a focus on graphical evaluation as well as early timepoint and median estimates of survival distributions.


Other Outcome Measures:
Immunologic correlative markers [ Time Frame: Up to day 28 ] [ Designated as safety issue: No ]
Will descriptively summarize the continuous markers quantitatively. Patterns of change in the longitudinal data on these markers will be evaluated in this manner for each of the correlative outcomes of interest. Appropriate transformations of the various correlative markers will be used in the presence of skewed data distributions. Multiple comparison corrections will not be used for these secondary correlative analyses.


Estimated Enrollment: 12
Study Start Date: March 2014
Estimated Primary Completion Date: August 2014 (Final data collection date for primary outcome measure

PRIMARY OBJECTIVES:

I. Determine safety and tolerability of reolysin (wild-type reovirus), carfilzomib and dexamethasone in patients with relapsed multiple myeloma.

II. Obtain evidence of reovirus protein production by immunohistochemical localization of reoviral capsid protein in myeloma cells from bone marrow biopsies obtained on cycle 1 day 9.

SECONDARY OBJECTIVES:

I. Obtain preliminary data on response as determined by International Myeloma Working Group criteria after protocol therapy.

II. Obtain pilot overall and progression free survival data for all treated patients.

III. Assess cytokine arrays of peripheral blood obtained on days 1, 2 and 9 to obtain exploratory data regarding inflammatory cytokine concentrations and their correlation with response.

IV. Cryopreserve marrow aspirates obtained cycle 1 day 1 and all subsequent marrow aspirates while on trial for future studies of genetic and epigenetic changes focused in part on endoplasmic reticulum (ER) stress, autophagy and reovirus resistance studies.

OUTLINE:

Patients receive dexamethasone intravenously (IV), carfilzomib IV over 10 minutes, and wild-type reovirus IV over 60 minutes on days 1, 2, 8, 9, 15, and 16. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 4 weeks and then every 6 months.